Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study.

OBJECTIVES/HYPOTHESIS: To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN: Cohort study. METHODS: A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS: Study participants (76% male, 60.4 ± 11.0 years old) had a body mass index of 29.2 ± 3.6 kg/m2 . AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS: The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1676-1682, 2021.

Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To compare patients with moderate-severe obstructive sleep apnea (OSA) undergoing traditional single and multilevel sleep surgery to those undergoing upper airway stimulation (UAS). STUDY DESIGN: Case control study comparing retrospective cohort of patients undergoing traditional sleep surgery to patients undergoing UAS enrolled in the ADHERE registry. SETTING: 8 multinational academic medical centers. SUBJECTS AND METHODS: 233 patients undergoing prior single or multilevel traditional sleep surgery and meeting study inclusion criteria were compared to 465 patients from the ADHERE registry who underwent UAS. We compared preoperative and postoperative demographic, quality of life, and polysomnographic data. We also evaluated treatment response rates. RESULTS: The pre and postoperative apnea hypopnea index (AHI) was 33.5 and 15 in the traditional sleep surgery group and 32 and 10 in the UAS group. The postoperative AHI in the UAS group was significantly lower. The pre and postoperative Epworth sleepiness scores (ESS) were 12 and 6 in both the traditional sleep surgery and UAS groups. Subgroup analysis evaluated those patients undergoing single level palate and multilevel palate and tongue base traditional sleep surgeries. The UAS group had a significantly lower postoperive AHI than both traditional sleep surgery subgroups. The UAS group had a higher percentage of patients reaching surgical success, defined as a postoperative AHI <20 with a 50% reduction from preoperative severity. CONCLUSION: UAS offers significantly better control of AHI severity than traditional sleep surgery. Quality life improvements were similar between groups.

Safety and efficacy of sphenopalatine ganglion stimulation for chronic cluster headache: a double-blind, randomised controlled trial.

BACKGROUND: Chronic cluster headache is the most disabling form of cluster headache. The mainstay of treatment is attack prevention, but the available management options have little efficacy and are associated with substantial side-effects. In this study, we aimed to assess the safety and efficacy of sphenopalatine ganglion stimulation for treatment of chronic cluster headache. METHODS: We did a randomised, sham-controlled, parallel group, double-blind, safety and efficacy study at 21 headache centres in the USA. We recruited patients aged 22 years or older with chronic cluster headache, who reported a minimum of four cluster headache attacks per week that were unsuccessfully controlled by preventive treatments. Participants were randomly assigned (1:1) via an online adaptive randomisation procedure to either stimulation of the sphenopalatine ganglion or a sham control that delivered a cutaneous electrical stimulation. Patients and the clinical evaluator and surgeon were masked to group assignment. The primary efficacy endpoint, which was analysed with weighted generalised estimated equation logistic regression models, was the difference between groups in the proportion of stimulation-treated ipsilateral cluster attacks for which relief from pain was achieved 15 min after the start of stimulation without the use of acute drugs before that timepoint. Efficacy analyses were done in all patients who were implanted with a device and provided data for at least one treated attack during the 4-week experimental phase. Safety was assessed in all patients undergoing an implantation procedure up to the end of the open-label phase of the study, which followed the experimental phase. This trial is registered with ClinicalTrials.gov, number NCT02168764. FINDINGS: Between July 9, 2014, and Feb 14, 2017, 93 patients were enrolled and randomly assigned, 45 to the sphenopalatine ganglion stimulation group and 48 to the control group. 36 patients in the sphenopalatine ganglion stimulation group and 40 in the control group had at least one attack during the experimental phase and were included in efficacy analyses. The proportion of attacks for which pain relief was experienced at 15 min was 62·46% (95% CI 49·15-74·12) in the sphenopalatine ganglion stimulation group versus 38·87% (28·60-50·25) in the control group (odds ratio 2·62 [95% CI 1·28-5·34]; p=0·008). Nine serious adverse events were reported by the end of the open-label phase. Three of these serious adverse events were related to the implantation procedure (aspiration during intubation, nausea and vomiting, and venous injury or compromise). A fourth serious adverse event was an infection that was attributed to both the stimulation device and the implantation procedure. The other five serious adverse events were unrelated. There were no unanticipated serious adverse events. INTERPRETATION: Sphenopalatine ganglion stimulation seems efficacious and is well tolerated, and potentially offers an alternative approach to the treatment of chronic cluster headache. Further research is need to clarify its place in clinical practice. FUNDING: Autonomic Technologies.

Previous Surgery and Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To examine whether previous palate or hypopharyngeal surgery was associated with efficacy of treatment of obstructive sleep apnea with hypoglossal nerve stimulation. STUDY DESIGN: Cohort (retrospective and prospective). SETTING: Eleven academic medical centers. SUBJECTS AND METHODS: Adults treated with hypoglossal nerve stimulation were enrolled in the ADHERE Registry. Outcomes were defined by the apnea-hypopnea index (AHI), in 3 ways: change in the AHI and 2 definitions of therapy response requiring ≥50% reduction in the AHI to a level <20 events/h (Response20) or 15 events/h (Response15). Previous palate and hypopharyngeal (tongue, epiglottis, or maxillofacial) procedures were documented. Linear and logistic regression examined the association between previous palate or hypopharyngeal surgery and outcomes, with adjustment for age, sex, and body mass index. RESULTS: The majority (73%, 217 of 299) had no previous palate or hypopharyngeal surgery, while 25% and 9% had previous palate or hypopharyngeal surgery, respectively, including 6% with previous palate and hypopharyngeal surgery. Baseline AHI (36.0 ± 15.6 events/h) decreased to 12.0 ± 13.3 at therapy titration (P < .001) and 11.4 ± 12.6 at final follow-up (P < .001). Any previous surgery, previous palate surgery, and previous hypopharyngeal surgery were not clearly associated with treatment response; for example, any previous surgery was associated with a 0.69 (95% CI: 0.37, 1.27) odds of response (Response20 measure) at therapy titration and a 0.55 (95% CI: 0.22, 1.34) odds of response (Response20 measure) at final follow-up. CONCLUSION: Previous upper airway surgery was not clearly associated with efficacy of hypoglossal nerve stimulation.

Post-approval upper airway stimulation predictors of treatment effectiveness in the ADHERE registry.

Upper airway stimulation (UAS) has been shown to reduce severity of obstructive sleep apnoea. The aim of this study was to identify predictors of UAS therapy response in an international multicentre registry.Patients who underwent UAS implantation in the United States and Germany were enrolled in an observational registry. Data collected included patient characteristics, apnoea/hypopnoea index (AHI), Epworth sleepiness scale (ESS), objective adherence, adverse events and patient satisfaction measures. Post hoc univariate and multiple logistic regression were performed to evaluate factors associated with treatment success.Between October 2016 and January 2018, 508 participants were enrolled from 14 centres. Median AHI was reduced from 34 to 7 events·h-1, median ESS reduced from 12 to 7 from baseline to final visit at 12-month post-implant. In post hoc analyses, for each 1-year increase in age, there was a 4% increase in odds of treatment success. For each 1-unit increase in body mass index (BMI), there was 9% reduced odds of treatment success. In the multivariable model, age persisted in serving as statistically significant predictor of treatment success.In a large multicentre international registry, UAS is an effective treatment option with high patient satisfaction and low adverse events. Increasing age and reduced BMI are predictors of treatment response.

Upper Airway Stimulation for Obstructive Sleep Apnea: Results from the ADHERE Registry.

Objective Upper airway stimulation (UAS) is an alternative treatment option for patients unable to tolerate continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA). Studies support the safety and efficacy of this therapy. The aim of this registry is to collect retrospective and prospective objective and subjective outcome measures across multiple institutions in the United States and Germany. To date, it represents the largest cohort of patients studied with this therapy. Study Design Retrospective and prospective registry study. Setting Ten tertiary care hospitals in the United States and Germany. Subjects and Methods Patients were included who had moderate to severe OSA, were intolerant to CPAP, and were undergoing UAS implantation. Baseline demographic and sleep study data were collected. Objective and subjective treatment outcomes, adverse events, and patient and physician satisfaction were reviewed. Results The registry enrolled 301 patients between October 2016 and September 2017. Mean ± SD AHI decreased from 35.6 ± 15.3 to 10.2 ± 12.9 events per hour ( P < .0001), and Epworth Sleepiness Scale scores decreased from 11.9 ± 5.5 to 7.5 ± 4.7 ( P < .0001) from baseline to the posttitration visit. Patients utilized therapy for 6.5 hours per night. There were low rates of procedure- and device-related complications. Clinical global impression scores demonstrated that the majority of physicians (94%) saw improvement in their patients' symptoms with therapy. The majority of patients (90%) were more satisfied with UAS than CPAP. Conclusions Across a multi-institutional registry, UAS therapy demonstrates significant improvement in subjective and objective OSA outcomes, good therapy adherence, and high patient satisfaction.

Drug-Induced Sleep Endoscopy.

Drug-induced sleep endoscopy (DISE) is an upper airway evaluation technique in which fiberoptic examination is performed under conditions of unconscious sedation. Unique information obtained from this 3-dimensional examination of the airway potentially provides additive benefits to other evaluation methods to guide treatment selection. This article presents recommendations regarding DISE technique and the VOTE Classification system for reporting DISE findings and reviews the evidence concerning DISE test characteristics and the association between DISE findings and treatment outcomes.

Acclimation settings with identical or similar sensation and functional thresholds.

Hypoglossal nerve stimulation with an activated implanted device does not awaken individuals from sleep once they have acclimated to the new sensation of the resulting tongue movement. This case report illustrates the importance of an acclimation period, allowing a patient to become accustomed to stimulation settings below the level at which there is gross tongue movement. Laryngoscope, 126:S20-S21, 2016.

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND: Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES: To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS: Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN: Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS: HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS: HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION: NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER: NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

Electrical stimulation of the hypoglossal nerve in the treatment of obstructive sleep apnea.

Upper airway occlusion in obstructive sleep apnea has been attributed to a decline in pharyngeal neuromuscular activity occurring in a structurally narrowed airway. Surgical treatment focuses on the correction of anatomic abnormalities, but there is a potential role for activation of the upper airway musculature, especially with stimulation of the hypoglossal nerve and genioglossus muscle. We present evidence from research on upper airway neuromuscular electrical stimulation in animals and humans. We also present results from eight obstructive sleep apnea patients with a fully implanted system for hypoglossal nerve stimulation, demonstrating an improvement in upper airway collapsibility and obstructive sleep apnea severity. Future research, including optimization of device features and stimulation parameters as well as patient selection, is necessary to make hypoglossal nerve stimulation a viable alternative to positive airway pressure therapy and upper airway surgical procedures.